1- -sparteine complexes substitution

The lithium-(-)-sparteine complex, generated by deprotonation of 1-methylindene, does not lose its configuration in diethyl ether solution even at room temperature80 presumably, the observed major diastcreonier is the thermodynamically determined product. Substitution with carbonyl compounds leads to 1-substituted (fl)-l-methyl-l//-indenes with >95% ee in high yields81. 

The a-substitution of enantiomerically enriched (-)-sparteine complexes of lithioalkenyl carbamates with methyl chloroformate76 or carbon dioxide77, in a manner contrary to a former assumption 76, proceeds with inversion of the configuration 131 131, leading to optically active 3-alkenoic acid esters. 

The TMEDA complex of a-lithiobenzyl iV,iV-diisopropylcarbamate was found to be configurationally stable on the microscopical scale in the Hoffmann test . The (—)-sparteine complex 222 has moderate configurational stability on the macroscopic scale, which could not been brought to useful selectivities in substitution reactions . As... 

Beak and coworkers found the (—)-sparteine-complex of iV-Boc-Af-(p-methoxyphe-nyl)benzyllithium 244, obtained from 243 by deprotonation with n-BuLi/(—)-sparteine (11) in toluene, to be configurationally stable (equation 57) . On trapping 244 with different electrophiles, the substitution products 245 are formed with high ee. Efficient addition reactions with imines and aldehydes have also been reported. The p-methoxyphenyl residue is conveniently removed by treatment with cerinm ammoninm nitrate (CAN). 

The lithium-(—)-sparteine complexes, derived from primary 2-alkenyl carbamates, are usually configurationally labile even at —78 °C. During the investigation of the (ii)-crotyl carbamate 301, the (—)-sparteine complex (5 )-302 crystallized in a dynamic thermodynamic resolution process (equation 76) and stereospecific substitutions could be performed with the slurry An incorrect assignment of the configuration of the lithium inter-... 

An X-ray crystal structure analysis was obtained from the 3-(trimethylsilyl)-aUyllithium-(—)-sparteine complex (5 )-302b. It reveals the monomeric structure of these aUyllithium compounds and a -coordination of the ally lie anion to the lithium cation. The latter is tetracoordinated and takes advantage of the chelating 0x0 group. The fixation of the lithium at the a-carbon atom is supposed to be the origin of the high regioselectivity of several substitution reactions. 

The asymmetric lithiation/substitution of Af-Boc-Af-(3-chloropropyl)-2-alkenylamines 395 by w-BuLi/(—)-sparteine (11) provides (5 )-Af-Boc-2-(alken-l-yl)pyrrolidines 397 via the allyllithium-sparteine complexes 396 (equation 106) . Similarly, the piperidine corresponding to 397 was obtained from the Af-(4-chlorobutyl)amine. Intramolecular epoxide openings gave rise to enantioenriched pyrrolidinols. Beak and coworkers conclude from further experiments that an asymmetric deprotonation takes place, but it is followed by a rapid epimerization a kinetic resolution in favour of the observed stereoisomer concludes the cyclization step. 

Cinnamate salts and cinnamic amides react with low regioselectivity to yield mixtures of the 2- and 3-alkylated products . orflzo-Substituted aryllithium-(-)-sparteine complexes 468 add with good enantiofacial discrimination to orf/zo-substituted ferf-butyl cinnamates 467 to give 469 (equation 128) ". The ehiral additive (i ,i )-l,2-dimethoxy-1,2-diphenylethane in some cases gave improved ee values. 

W-Substituted 2,4-alkadien-l-ols such as 474 add the alkyllithium/(—)-sparteine complex preferentially to the 2-position to form via the alkoxide the corresponding allyllithium intermediates 475 . Protic workup leads to a mixture of ii/Z-alkenols 476 and 477 on catalytic hydrogenation the -branched alcohols 478 are isolated (equation 130). 

Enantioenriched a-carbamoyloxy allylic stannanes can be prepared by lithiation of allylic carbamates in the presence of (-)-sparteine (Eq. 42) [62]. Ilie resulting lithiated sparteine complex reacts with BuaSnLi at the a-position to afford the substitution product. The crotyl derivative of 80% ee is thus prepared. This stannane undergoes thermal addition to benzaldehyde at 160 °C to afford the anti- S) adduct of 79% ee in 79% yield. 

Treatment of A-Boc pyrrolidine 29 with the 5 -BuLi/(—)-sparteine complex followed by reaction with BFs-activated ethylene oxide leads to the formation of 2-substituted pyrrolidine 30 in high yield and modest enantioinduction (eq 47). ... 

Since carbohthiations usually proceed as syn additions, 458 is expected to be formed first. Due to the configurationally labile benzylic centre it epimerizes to the trani-substitu-ted chelate complex epi-45S. The substitution of epi-458 is assumed to occur with inversion at the benzylic centre. Sterically more demanding reagents (t-BuLi) or the well-stabilized benzyllithium do not add. The reaction works with the same efficiency when other complexing cinnamyl derivatives, such as ethers and primary, secondary, or tertiary amines, are used as substrates . A substoichiometric amount (5 mol%) of (—)-sparteine (11) serves equally well. The appropriate (Z)-cinnamyl derivatives give rise to ewf-459, since the opposite enantiotopic face of the double bond is attacked . 

Oeeasionally, very good enantioselectivities were achieved in the (-)-sparteine-mediated carbolithiation of 6-dimethylaminofulvene (470) by ort/zo-substituted aiyllithiums 471 (equation 129) . Here, (—)-sparteine (11) turned out the best chiral additive. The lithium cyclopentadienides 472 were converted to the corresponding Rh(l)-norbornadiene complexes 473. 

A similar effect controls the lithiation and substitution of the benzylic carbamate 86.33 35 Lithiation of 86 with s-BuLi-(-)-sparteine in ether gives low enantiomeric excesses, but when the lithiation is carried out in hexane, a solvent in which the intermediate complex is not soluble, the enantiomeric excess of the product 88 increases to 82%. Even higher enantiomeric excesses are obtained if the intermediate suspension of organolithium-(-)-... 

The formation of diastereoisomerically pure complexes of 90 with (-)-sparteine is also controlled by crystallisation. Treatment of the indene 89 with BuLi and (-)-sparteine in ether gives, on warming, a yellow precipitate which reacts with carbonyl electrophiles to provide the products 91 typically with good regioselectivity and >95% ee.52 An X-ray crystal structure proved the stereochemistry of the intermediate complex to be that shown as 90b, and hence proved the stereochemical course of the substitution (see section 6.1). The complex is readily decomposed by THF, in the presence of which it rearranges to a racemic V allyllithium. 

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